Dust formation around AGB and SAGB stars: a trend with metallicity?

We calculate the dust formed around AGB and SAGB stars of metallicity Z=0.008 by following the evolution of models with masses in the range 1M<M<8M throughthe thermal pulses phase, and assuming that dust forms via condensation of molecules within a wind expanding isotropically from the stellar surface. We find that, because of the strong Hot Bottom Burning (HBB) experienced, high mass models produce silicates, whereas lower mass objects are predicted to be surrounded by carbonaceous grains; the transition between the two regimes occurs at a threshold mass of 3.5M. These fndings are consistent with the results presented in a previous investigation, for Z=0.001. However, in the present higher metallicity case, the production of silicates in the more massive stars continues for the whole AGB phase, because the HBB experienced is softer at Z=0.008 than at Z=0.001, thus the oxygen in the envelope, essential for the formation of water molecules, is never consumed completely. The total amount of dust formed for a given mass experiencing HBB increases with metallicity, because of the higher abundance of silicon, and the softer HBB, both factors favouring a higher rate of silicates production. This behaviour is not found in low mass stars,because the carbon enrichment of the stellar surface layers, due to repeated Third Drege Up episodes, is almost independent of the metallicity. Regarding cosmic dust enrichment by intermediate mass stars, we find that the cosmic yield at Z=0.008 is a factor 5 larger than at Z=0.001. In the lower metallicity case carbon dust dominates after about 300 Myr, but at Z=0.008 the dust mass is dominated by silicates at all times,with a prompt enrichment occurring after about 40 Myr, associated with the evolution of stars with masses M =7.5 -8M.Comment: 14 pages, 10 figures, 2 Tables, accepted for publication in MNRA

Turbulence-driven Polar Winds from T Tauri Stars Energized by Magnetospheric Accretion

Pre-main-sequence stars are observed to be surrounded by both accretion flows and some kind of wind or jet-like outflow. Recent work by Matt and Pudritz has suggested that if classical T Tauri stars exhibit stellar winds with mass loss rates about 0.1 times their accretion rates, the wind can carry away enough angular momentum to keep the stars from being spun up unrealistically by accretion. This paper presents a preliminary set of theoretical models of accretion-driven winds from the polar regions of T Tauri stars. These models are based on recently published self-consistent simulations of the Sun's coronal heating and wind acceleration. In addition to the convection-driven MHD turbulence (which dominates in the solar case), we add another source of wave energy at the photosphere that is driven by the impact of plasma in neighboring flux tubes undergoing magnetospheric accretion. This added energy, determined quantitatively from the far-field theory of MHD wave generation, is sufficient to produce T Tauri-like mass loss rates of at least 0.01 times the accretion rate. While still about an order of magnitude below the level required for efficient angular momentum removal, these are the first self-consistent models of T Tauri winds that agree reasonably well with a range of observational mass loss constraints. The youngest modeled stellar winds are supported by Alfven wave pressure, they have low temperatures ("extended chromospheres"), and they are likely to be unstable to the formation of counterpropagating shocks and clumps far from the star.Comment: 19 pages (emulateapj style), 13 figures, ApJ, in press (v. 689, December 10, 2008

Efficacious Recombinant Influenza Vaccines Produced by High Yield Bacterial Expression: A Solution to Global Pandemic and Seasonal Needs

It is known that physical linkage of TLR ligands and vaccine antigens significantly enhances the immunopotency of the linked antigens. We have used this approach to generate novel influenza vaccines that fuse the globular head domain of the protective hemagglutinin (HA) antigen with the potent TLR5 ligand, flagellin. These fusion proteins are efficiently expressed in standard E. coli fermentation systems and the HA moiety can be faithfully refolded to take on the native conformation of the globular head. In mouse models of influenza infection, the vaccines elicit robust antibody responses that mitigate disease and protect mice from lethal challenge. These immunologically potent vaccines can be efficiently manufactured to support pandemic response, pre-pandemic and seasonal vaccines

Meridional circulation in turbulent protoplanetary disks

Based on the viscous disk theory, a number of recent studies have suggested there is large scale meridional circulation in protoplanetary disks. Such a flow could account for the presence of crystalline silicates, including calcium- and aluminum-rich inclusions (CAIs), at large distances from the sun. This paper aims at examining whether such large-scale flows exist in turbulent protoplanetary disks. High-resolution global hydrodynamical and magnetohydrodynamical (MHD) numerical simulations of turbulent protoplanetary disks were used to infer the properties of the flow in such disks. By performing hydrodynamic simulations using explicit viscosity, we demonstrate that our numerical setup does not suffer from any numerical artifact. The aforementioned meridional circulation is easily recovered in viscous and laminar disks and is quickly established. In MHD simulations, the magnetorotational instability drives turbulence in the disks. Averaging out the turbulent fluctuations on a long timescale, the results fail to show any large-scale meridional circulation. A detailed analysis of the simulations show that this lack of meridional circulation is due to the turbulent stress tensor having a vertical profile different from the viscous stress tensor. A simple model is provided that successfully accounts for the structure of the flow in the bulk of the disk. In addition to those results, possible deviations from standard vertically averaged alpha disk models are suggested by the simulations and should be the focus of future work. Global MHD numerical simulations of fully ionized and turbulent protoplanetary disks are not consistent with the existence of a large-scale meridional flow. As a consequence, the presence of crystalline silicates at large distance for the central star cannot be accounted for by that process as suggested by recent models based on viscous disk theory.Comment: 16 pages, 13 figures, changes according to referee report. Accepted to Astronomy and Astrophysic

Genome sequencing and carrier testing: decisions on categorization and whether to disclose results of carrier testing

We are investigating the use of genome sequencing for preconception carrier testing. Genome sequencing could identify one or more of thousands of X-linked or autosomal recessive conditions that could be disclosed during preconception or prenatal counseling. Therefore, a framework that helps both clinicians and patients understand the possible range of findings is needed to respect patient preferences by ensuring that information about only the desired types of genetic conditions are provided to a given patient

Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals

We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57

World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions

BACKGROUND: To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. METHODS: In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40-80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. FINDINGS: Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0·685 (95% CI 0·629-0·741) to 0·833 (0·783-0·882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40-64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. INTERPRETATION: We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide. FUNDING: World Health Organization, British Heart Foundation (BHF), BHF Cambridge Centre for Research Excellence, UK Medical Research Council, and National Institute for Health Research

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes